title: Mesocortical dopamine system modulates mechanical nociceptive responses recorded in the rat prefrontal cortex.
abstract: BACKGROUND
  Psychological conditions affect pain responses in the human anterior cingulate cortex (ACC) according to brain imaging analysis. The rodent prefrontal cortex (PFC) including cingulate areas is also related to the affective dimension of pain. We previously reported PFC nociceptive responses inhibited by inputs from the amygdala, such as with dopamine (DA) D2 receptor (D2R) blockers, to show decreased effect on amygdala projections. In this study, we examined whether direct projections from the ventral tegmental area (VTA) to the PFC affect nociceptive responses in the PFC.
  
  
  RESULTS
  High frequency stimulation (HFS, 50 Hz, 30 s) delivered to the VTA produced long-lasting suppression (LLS) of nociceptive responses in the rat PFC including cingulate and prelimbic areas. Nociceptive responses evoked by mechanical pressure stimulation (2 s duration at 500 g constant force) applied to the tails of urethane-anesthetized rats were recorded using extracellular unit recording methods in the PFC. HFS delivered to the VTA, which has been reported to increase DA concentrations in the PFC, significantly suppressed nociceptive responses. The LLS of nociceptive responses persisted for about 30 minutes and recovered to the control level within 60 min after HFS. We also demonstrated local microinjection of a selective D2 agonist of DA receptors to induce LLS of mechanical nociceptive responses, while a D2 but not a D1 antagonist impaired the LLS evoked by HFS. In contrast, DA depletion by a 6-hydroxydopamine injection or a low concentration of DA induced by a κ-opiate receptor agonist injected into the VTA had minimal effect on nociceptive responses in the PFC.
  
  
  CONCLUSIONS
  HFS delivered to VTA inhibited nociceptive responses for a long period in PFC. DA D2R activation mediated by local D2 agonist injection also induced LLS of mechanical nociceptive responses. The mesocortical DA system may modify PFC nociceptive responses via D2 activity.
authors.affiliation: Department of Physiology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sogabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yagasaki
authors.forename: Kitaro
authors.initials: K
authors.lastname: Onozawa
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001703:Biophysics; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation / Q000009:adverse effects; D007839:Functional Laterality; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000378:metabolism* / Q000503:physiopathology*; D059226:Nociceptive Pain / Q000209:etiology / Q000473:pathology*; D010812:Physical Stimulation / Q000009:adverse effects; D017397:Prefrontal Cortex / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D015259:Dopamine Agents; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004298:Dopamine